Pumilio2, but not Pumilio1, expression is significantly increased in high-grade and metastatic gastroenteropancreatic neuroendocrine neoplasms.

Pumilio proteins (PUM1 and PUM2) are evolutionarily conserved RNA-binding proteins that regulate gene expression at the post-transcriptional level and have been implicated in tumourigenesis in various cancers. However, their role in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has not been previously investigated. This study aimed to evaluate the expression of PUM1 and PUM2 in GEP-NENs and determine their association with tumour grade and metastatic status. Transcriptomic data (GSE98894) were analyzed using GEO2R to assess differential gene expression in primary tumours, lymph node metastases, and distant meta- stases. Additionally, immunohistochemical analyses were performed on formalin- fixed paraffin-embedded samples, and protein expression was quantified using digital image analysis. Statistical comparisons were conducted across tumour sites and grades (G1-G3). At the mRNA level, PUM2 was significantly upregulated in distant metastases compared with primary tumours (log2FC = 0.151; adjusted p = 0.024), whereas PUM1 showed no significant difference. Protein-level analyses confirmed expression of both proteins in all samples; however, only PUM2 was significantly elevated in high-grade (G3) tumours compared to G1/G2. These findings suggest that PUM2, but not PUM1, is associated with tumour progression in GEP-NENs, although a causal role remains to be established.